Automated tissue staining system and reagent container

ABSTRACT

An automated staining system and a reagent container designed for use with the automated staining apparatus. The reagent container includes a reagent containment section capable of containing a volume of a reagent. The reagent containment section includes an upper wall and a base wall that are spaced apart along an axis. The base wall includes a well having a nadir that is aligned axially with an access opening in the upper wall so that a reagent probe entering the opening parallel to the axis will travel toward the nadir. In another aspect of the invention, the reagent container may include a two-dimensional data element containing reagent information. The staining apparatus may include one removable drawer for holding reagent containers and another removable drawer holding slides.

CROSS-REFERENCE

This application is a continuation of U.S. patent application Ser. No.13/041,608, filed Mar. 7, 2011, now issued as U.S. Pat. No. 8,142,739 onMar. 27, 2012, which is a continuation of U.S. patent application Ser.No. 12/644,705, filed Dec. 22, 2009, now issued as U.S. Pat. No.7,901,941 on Mar. 8, 2011, which is a divisional of U.S. patentapplication Ser. No. 12/250,116, filed Oct. 13, 2008, now issued as U.S.Pat. No. 7,642,093 on Jan. 5, 2010, which is a divisional of U.S. patentapplication Ser. No. 11/351,159, filed Feb. 9, 2006, now issued as U.S.Pat. No. 7,435,383 on Oct. 14, 2008, which is a divisional of U.S.patent application Ser. No. 09/994,458, filed Nov. 26, 2001, now issuedas U.S. Pat. No. 6,998,270 on Feb. 14, 2006, the disclosures of whichare hereby incorporated herein by reference in their entireties.

FIELD OF THE INVENTION

The invention relates generally to an automated tissue staining systemand reagent containers for use with the system.

BACKGROUND OF THE INVENTION

Laboratories routinely stain tissue specimens for the purpose ofdetecting and/or monitoring tissue abnormalities. An automated tissuestaining system allows batch staining of large numbers of tissuespecimens for subsequent examination. Automation of the staining processsignificantly reduces the time required to stain tissue specimens,reduces the incidence of human error incipient in manual staining, andallows processing parameters to be altered in an efficient manner.

The staining process requires various types of reagents that are addedto a slide carrying a tissue specimen. Reagents are an expensiveexpendable commodity. In a typical automated staining apparatus, thereagents are typically aspirated with a reagent probe from a reagentcontainer and delivered to the tissue specimen on each slide. Foraccurate reagent dispensing, the reagent container contains an excessvolume of reagent beyond a volume required for the staining process. Theexcess volume is required so that the reagent probe can aspirate therequired volume from the reagent container. Conventional reagentcontainers are not configured to optimize the amount of reagent that thereagent probe successfully can withdraw and, thereby, to minimize theamount of reagent wasted.

A conventional automatic staining apparatus typically requires a set-upsequence to enter reagent parameters such as lot number, reagentidentity, expiration date, reagent volume, reagent incompatibilities,and the like. Some reagent containers have a one-dimensional bar codethat contains this or a subset of this reagent information. Reading thereagent information with a bar code reader and providing thatinformation to the control system operating the staining apparatusreduces the time required to program a staining run. However,one-dimensional bar codes capable of holding a complete set of reagentparameters are too large to be placed on the reagent containers commonlyused in automatic staining apparatus.

The automated staining apparatus has a processing space in which theenvironment is tightly controlled during the staining run. If additionalslides are to be added to the pending slides in a staining run, the usermust pause the staining run and breach the controlled environment of theprocessing space to add the new slides. The reagent containers are alsopositioned within the processing space. If new slides are added, theuser must modify the types and/or quantities of reagents to satisfy therequirements of the global staining protocols of all slides by againbreaching the processing space. Therefore, the lab techniciancompromises or otherwise disrupts the integrity of the controlledenvironment in the processing space when slides are added to a currentlyexecuting staining run.

During a staining run, the tissue specimens are exposed to a series ofwell-defined processing steps or a protocol that ultimately produces aproperly stained specimen for examination. Conventionally, the automatedstaining apparatus may store the protocol or, in the alternative, maymemorialize the protocol by a printed hard copy. Conventional automatedstaining devices cannot provide or export the protocol directly to apatient record database or laboratory information system so that, shoulda question arise regarding the protocol used to stain a specific tissuespecimen, the complete association is readily available in a singledatabase.

SUMMARY OF THE INVENTION

According to the present invention, apparatus and methods are providedfor staining tissue specimens using an autostainer. A reagent containercapable of containing a volume of a reagent for use with the automatedstaining apparatus, which container includes an upper wall, a base walland a tubular side wall interconnecting the upper and base walls tocollectively define an internal reagent holding chamber, the upper andbase walls being spaced from each other along an imaginary lineintersecting the upper and base walls. The base wall includes a cavitycommunicating with the lowermost portion of the holding chamber. Theupper wall has an access opening in the upper wall aligned with thecavity along the imaginary line so that a reagent probe entering theopening parallel in a direction to said imaginary line will traveltoward said cavity bottom, the lowermost portion of said holdingchamber.

In another aspect of the invention, the reagent container may include atwo-dimensional data element containing reagent information. In yetanother aspect of the invention, the staining apparatus may include aremovable drawer for holding a reagent rack filled with reagentcontainers and a separate removable drawer holding slide racks.

These and other advantages, objectives, and features of the inventionwill be apparent in light of the following figures and detaileddescription.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of an automatic staining apparatus of thepresent invention, shown with the lid removed.

FIG. 1A is a diagrammatic view of the Z-head of FIG. 1.

FIG. 2 is a top view of the automatic staining apparatus of FIG. 1.

FIG. 3 is a perspective view of the automatic staining apparatus of FIG.1, shown with the slide and reagent drawers withdrawn.

FIG. 4 is a diagrammatic view of the fluid dispensing system for theautomatic staining apparatus of FIG. 1.

FIG. 5 is a perspective view of the reagent rack of FIG. 1.

FIG. 6 is a cross-sectional view of one of the reagent containers ofFIG. 1.

FIG. 6A is a cross-sectional view taken generally along line 6A-6A ofFIG. 6.

FIG. 7 is a bottom view of the reagent container of FIG. 6.

FIG. 7A is a bottom view of an alternative embodiment of the reagentcontainer of the present invention.

FIG. 8 is a side view of the reagent container of FIG. 6, shownpositioned on a flat surface.

FIG. 9 is a top view of the reagent container of FIG. 6.

FIG. 10 is a cross-sectional view of another embodiment of a reagentcontainer of the present invention.

FIG. 11 is a perspective view of another embodiment of a reagentcontainer of the present invention.

DETAILED DESCRIPTION

To remedy the aforementioned deficiencies of conventional automatedtissue staining devices, the present invention provides an apparatus forautomatically staining tissue specimens carried by slides according tovarious staining protocols and a reagent container that significantlyreduces the amounts of wasted reagents. As used hereinafter, the term“staining” includes, but is not limited to, reagent uptake, chemicalreaction, localization (e.g., antigen-antibody associations),radioactive activation, and the like.

With reference to FIGS. 1, 2, and 3, the present invention comprises anautomatic staining apparatus or autostainer 10 used for staining orotherwise reacting reagents with the cells of tissue specimens mountedon slides 12. The autostainer 10 includes a chassis 14 and a cover orlid 16 (FIG. 3), hinged along its rear horizontal edge, thatcollectively define a processing space 18 having a controlledenvironment, such as a controlled humidity. The lid 16 isolates thecontrolled environment of the processing space 18 from the surroundingambient environment 17. Lid 16 may be optically transparent so that auser can observe events transpiring in the processing space 18. The lid16 may also be hinged for cantilevering or moving the lid 16 between anopen condition, indicated in solid lines in FIG. 3, and a closedcondition, shown in phantom in FIG. 3. The lid 16 makes a sealingengagement with a seal 15 provided on the chassis 14 so as toparticipate in providing the controlled environment in processing space18.

A plurality of slides 12 are held by a plurality of, for example, threeslide racks 20 mounted in the processing space 18. Each of the threeslide racks 20 holds, for example, twelve individual slides 12 so thatthe automatic staining apparatus can stain one or more tissue specimensmounted on a total of thirty-six slides 12. Typically, the clips (notshown) for holding the slides 12 contact only an unused region thereof,such as a frosted marginal region.

With continued reference to FIGS. 1, 2, and 3, the autostainer 10includes an X-Y-Z robotic delivery system 22 that is capable ofdelivering bulk reagents, small supply reagents, buffer solutions, andair to the tissue specimens on the slides 12. The X-Y-Z robotic deliverysystem 22 includes a Z-head 24 that is controllably and selectivelymovable on a pair of linear motion assemblies, indicated generally byreference numerals 26 a and 26 b to any position in a horizontal X-Yplane. The Z-head 24 carries a vertically disposed probe 38, which isselectively and controllably movable up and down in a vertical, or Z,direction. An exemplary X-Y-Z robotic delivery system, similar todelivery system 22, is described in commonly-assigned U.S. Pat. No.5,839,091 and in copending, commonly assigned U.S. patent applicationSer. No. 09/483,248, filed on Jan. 14, 2000, now U.S. Pat. No.6,746,851, and entitled “Method and Apparatus for Automatic TissueStaining,” the disclosure of each being expressly incorporated byreference herein in its entirety.

The operation of the autostainer 10, including the operation of therobotic delivery system 22, is controlled by an autostainer controlprogram implemented by the software of a control system 28. The hardwareof the control system 28 is integrated into the chassis 14 of theautostainer 10 and includes a touchscreen display 30. Touchscreendisplay 30 is a computer input device for viewing information andinputting information, as understood by those of ordinary skill in theart. Alternatively, various items of information may be viewed andentered remotely from the chassis 14. Because the control system 28 isintegrated into the chassis 14, the autostainer 10 does not require anexternal microprocessor, such as a conventional personal computer, foroperation and constitutes a self-contained stand-alone unit.

The control system 28 includes a data storage unit or medium for storinginformation, such as staining protocols, and retrieving that storedinformation on demand. The control system 28 is interfaced by acommunication link 31, such as a local area network, so that theautostainer 10 may exchange information with another information storagedevice 32, such as another laboratory instrument or a remote computersystem. For example, the control system 28 may be capable of exporting astaining record containing information such as the staining protocol,reagent information, and the like to the information storage device 32over the communications link 31. The information storage device 32 wouldassociate the staining record with existing patient information in apatient record database or a laboratory information system and provide,associate, and/or store the staining record with that information forfuture report generation. The information storage device may alsoperform statistical analysis on multiple staining records to, forexample, determine compliance with regulatory standards.

The control system 28 is also capable of importing or retrievinginformation from the information storage device 32 via communicationslink 31. The imported information may comprise a staining recordcontaining protocol information that the control system 28 can use as atemplate for staining one or more of the slides 12. The ability toimport the staining protocol from device 32 precludes manually inputtingthe information using touchscreen display 30. The imported informationmay also include patient information, which may be associated with thestaining protocol and/or stored by the control system 28. One use forthe associated patient record and staining protocol, whether residing oncontrol system 28 or on information storage device 32, is qualitycontrol and quality assurance documentation.

With reference to FIGS. 1, 1A and 4, the Z-head 24 of the roboticdelivery system 22 carries a fluid dispensing system 34 having a bulkfluid dispensing tube 36, a reagent probe 38, and an air blade 40. Thebulk fluid dispensing tube 36 is capable of dispensing buffer solutionfrom a buffer supply (not shown) delivered by supply line 41 or reagentsdelivered via supply lines 42 and 43 from internal bulk reagent supplies(not shown), as selected by a distribution valve 44. The reagent probe38 is capable of aspirating a small quantity of a specific reagent fromone of a plurality of reagent containers 50 using suction generated by areagent syringe pump 46 and then dispensing that reagent at a specificlocation on a specific slide 12. Air blade 40 is capable of selectivelydirecting a flow of air delivered by supply line 48 from a compressedair supply (not shown) used to dry slides 12.

The Z-head 24 of the robotic delivery system 22 is equipped with avertical drive assembly (not shown) operably coupled with the reagentprobe 38 for controllably and selectively moving the probe 38 up anddown in the vertical Z-direction. The vertical positions of the airblade 40 and the bulk fluid dispensing tube 36 are independently movablein the vertical Z-direction using a different vertical drive assembly(not shown) also disposed within the Z-head 24. The vertical driveassemblies are utilized to position the bulk fluid dispensing tube 36,reagent probe 38, and air blade 40 relative to the slides 12 and toposition the reagent probe 38 relative to a wash bin 52 (FIGS. 1-3). Aprocedure for cleaning the reagent probe 38 using wash bin 52 isdescribed in U.S. Pat. No. 5,839,091 incorporated by reference above.

With reference to FIGS. 1 and 2, the reagent probe 38 is cleaned in thewash bin 52 to remove residual traces of a reagent when a differentreagent is to be aspirated from one of the reagent containers 50 anddispensed onto one or more of the slides 12. The practice of cleaningthe reagent probe 38 lessens or eliminates the likelihood ofcross-contamination and may be incorporated as process steps into theprogramming of the control system 28 of the autostainer 10. The wash bin52 has three individual receptacles 53, 54, and 55 used in a sequence ofthree wash stages. The operation of wash bin 52 for cleaning the reagentprobe 38 is described in U.S. Pat. No. 5,839,091 incorporated byreference above. Liquid waste, such as spent reagents and buffer rinsesolution that drain from the slides 12, is captured by a sink assembly58.

The autostainer control system 28 implements software that accepts andeffectuates a series of process steps or staining protocol for stainingthe tissue specimen mounted on each slide 12. The autostainer 10optimizes the order of protocol execution and executes the stainingprotocols by providing a series of instructions to the robotic deliverysystem 22. The execution may be paused to add slides 12 carryingprioritized or “stat” tissue specimens to the slide racks 20 and tointegrate their staining protocols with the staining protocols of theslides 12 pending when the staining process was paused. Such protocolprogramming is described in U.S. Pat. No. 5,839,091 and patentapplication Ser. No. 09/483,248, now U.S. Pat. No. 6,746,851,incorporated by reference above, and in commonly assigned U.S. patentapplication Ser. No. 10/010,830, now U.S. Pat. No. 6,735,531, entitled“Method and Apparatus for Automatic Tissue Staining,” which is expresslyincorporated by reference herein in its entirety.

With reference to FIGS. 1-3 and 5, each of the small supply reagents iscontained within one of the reagent containers 50. The reagentcontainers 50 are held in a reagent rack 67 that is disposed within areagent drawer 68. Similarly, the slide racks 20 and sink assembly 58are held within a slide drawer 70. The reagent drawer 68 and the slidedrawer 70 are each independently slidably mounted for selective “in” and“out” movement in the Y-direction in a conventional manner relative tothe chassis 14, such as with drawer slides. Reagent drawer 68 has aclosed position (FIG. 1) in which the reagent containers 50 arepositioned in the processing space 18 and an open position (FIG. 3) inwhich the reagent rack 67 is positioned outside of the processing space18 and accessible externally of the chassis 14. A portion of seal 15 issuspended on a horizontal frame member 60 (FIG. 3) extending between theopposite side edges of the chassis 14.

As illustrated in FIG. 2, the reagent drawer 68 may be horizontallywithdrawn in the Y direction from the closed position (FIG. 1) to theopen position (FIG. 3) so as to permit access to the reagent rack 67.The withdrawal of the reagent drawer 68 may be accomplished manually orwith the assistance of an actuator. This permits reagents to be added toindividual reagent containers 50 already positioned in the reagent rack67 and/or new reagent containers 50 to be added to rack 67.Alternatively, the reagent rack 67 may be removed from the reagentdrawer 68 for addition of reagents and/or reagent containers 50 and,thereafter, returned to drawer 68. After the reagent inventory isadjusted by either adding reagents or reagent containers 50, the reagentdrawer 68 is returned to the closed position. Similarly, the slidedrawer 70 may be withdrawn in a horizontal, Y direction from the chassis14 of the autostainer 10 to permit access to the slides 12 held by theslide racks 20 for removal or addition. This permits a user-convenientand independent access to the slides 12 and/or reagent containers 50 inthe autostainer 10.

The drawers 68, 70 facilitated the exchange of slides 12 while limitingthe impact of the exchange on the controlled environment within theprocessing space 18. In particular, the drawers 68, 70 permit theaddition of slides 12, such as slides 12 carrying “stat” tissuespecimens, quantities of reagent, and reagent containers 50 to theprocessing space 18, while limiting the impact of the exchange on thecontrolled environment within the processing space 18. It is appreciatedthat lid 16 is maintained in a closed condition, including instances inwhich the drawers 68, 70 are withdrawn from chassis 14, except forexceptional circumstances such as performing maintenance on autostainer10. As a result, the lid 16 participates in isolating the processingspace 18 from the environment surrounding the autostainer 10.

With reference to FIG. 5 and in the illustrated embodiment, the reagentrack 67 includes a generally planar platform 72, a pair of spaced-apartsupports 74, 75 projecting downward from opposite sides of the platform72, and a plurality of apertures 76 each consisting of a substantiallyrectangular bore extending through the platform 72. Each of theapertures 76 is shaped and dimensioned to accept and hold the reagentcontainers 50 of the invention. Each reagent container 50 is suspendedon a pair of outwardly-projecting flanges 106 a, 106 b that contact theplatform 72 and prevent vertically downward movement of the container 50relative to platform 72. The locations of the apertures 76 in the arrayare well-defined so that the reagent containers 50 are preciselypositioned for reference by the control system 28.

The platform 72 of the reagent rack 67 is elevated by the spaced-apartsupports 74, 75 so that each reagent container 50 is suspended above theunderlying and confronting upper surface of the bottom of theautostainer 10. The elevation of reagent container 50 preventsapplication of a force that would otherwise displace the container 50vertically relative to its aperture 76. Specifically, a base wall 90(FIG. 6) of the reagent container 50 has a non-contacting relationshipwith the underlying and confronting upper surface of the bottom of theautostainer 10. Alternatively, the reagent rack 67 may permit reagentcontainer 50 to contact the underlying upper surface of the bottom ofthe autostainer 10 if the applied vertical displacement force is nil ornegligible. It is appreciated that the platform 72 may be supported bysupports 74, 75 of differing configuration or otherwise supported in anymanner that eliminates or minimizes any applied vertical displacementforce.

With reference to FIG. 6, the reagent container 50 includes a reagentcontainment section 80 that holds a volume of a reagent within aninternal reagent chamber 105, a hollow neck 82, a circular opening 84 atthe top of the neck 82 providing access to the reagent containmentsection 80, and a closure 86 removably attached to the neck 82 forsealing the opening 84 against accidental spillage of the reagent andentry of contamination. The reagent containment section 80 includes anupper wall 88, the base wall 90, a rear wall 92 having a shallowV-shape, a pair of side walls 94 and 96, and a curved front wall 98. Therear wall 92, side walls 94, 96 and front wall 98 collectivelyconstitute a tubular side wall which interconnects the upper wall 88with the base wall 90. The corner edges 99, 100 at the intersection orjunction of the side walls 94, 96 with the opposite edges of the rearwall 92 are rounded with a small radius. The reagent container 50 has amirror symmetry about a plane bisecting the rear and front walls 92, 98.The upper wall 88 is vertically spaced from the base wall 90 along animaginary vertical line 101 which passes through, and preferably issymmetrically disposed with respect to, the tubular neck 82. Theimaginary vertical line 101 also preferably passes through the lowermostportion of the reagent chamber 105 at nadir 104, as discussed in moredetail below.

With reference to FIGS. 6, 6A and 7 and according to one preferredaspect of the invention, the base wall 90 converges downwardly andinwardly from each of the side walls 94, 96, the rear wall 92 and thefront wall 98 to define a concave, polyhedral cavity or well 102communicating with the regent chamber 105. For reasons discussedhereafter, the existence of the well 102, and its spatial orientationwith respect to the neck 84 and the imaginary line 101, increases theefficiency of reagent extraction from the reagent containment section90. As shown in FIG. 7, the base wall 90 of the reagent container 50includes four wall showing sections 80 a-d that converge inwardly towardthe nadir 104. The nadir 104 is a seam formed at the junction of theinner surfaces 80 a′ and 80 d′ of wall section 80 a and wall section 80d, respectively. The nadir 104 is rounded with a narrow radius ofcurvature. Wall sections 80 b and 80 c taper inwardly from theirrespective boundaries with the side walls 94 and 96 for bounding thelength of the nadir 104. In one embodiment, each of the inner surfaces80 b′ and 80 c′ of wall sections 80 b and 80 c, respectively, tapersinwardly toward the nadir 104 at an angle of about 45° with respect toan imaginary vertical plane passing perpendicularly through nadir 104.

With continued reference to FIGS. 6, 6A and 7, well 102 of base wall 90has a reduced horizontal cross-sectional area relative to the horizontalcross-sectional area of the reagent chamber 105, with the minimumhorizontal cross-sectional area occurring near the nadir 104. The well102 provides a reservoir of decreasing surface area as the volume ofreagent within container 50 is expended by successive aspirations andthe reagent fluid level within the reagent containment section 80decreases below the lower horizontal edges of the walls 92, 94, 96, 98toward the nadir 104. When the residual reagent no longer wets the walls92, 94, 96, 98, the effective liquid surface area of the reagent in well102 and facing the opening 84 decreases as the reagent is consumed.However, the enhanced fluid level or effective depth of the reagent inwell 102 near the nadir 104 permits the decreasing volume of residualreagent to have a maximized effective depth for aspiration and deliveryof the required volume by the reagent probe 38. In other words, theresidual reagent in well 102 of reagent container 50 has a relativelyhigh volume-to-surface ratio compared to conventional reagent containershaving flat or relatively flat base walls. The high volume-to-surfaceratio permits each reagent container 50 of the invention to be filledwith less excess volume of reagent beyond the volume required for thestaining run. The excess volume of reagent represents a minimumeffective depth in reagent chamber 105 for which the reagent probe 38can successfully aspirate reagent and remains in the container 50 afterthe reagent therein is dispensed during the staining run.

The reagent chamber 105 of reagent container 50, including well 102,holds a specific maximum volume of a reagent, typically about 15 ml, orany volume less than the maximum volume, which includes the excessvolume described above. As the reagent is dispensed from the reagentcontainer 50 by the autostainer 10, the fluid level or residual volumeof the reagent in the interior 105 gradually drops. Eventually, enoughreagent is dispensed from the interior 105 such that the only theresidual reagent with reagent container 50 is confined in well 102 andhas a volume greater than or equal to the excess volume. Because of thepresence of well 102 and in one embodiment, reagent can be aspiratedsuccessfully from the reagent container 50 for an excess volume ofresidual reagent as small as about 0.1 ml. Therefore, reagent container50 requires an excess volume of reagent in well 102 of only about 0.1ml.

With continued reference to FIGS. 6, 6A and 7, the circular opening 84in neck 82 is configured and dimensioned so that the reagent probe 38can extend vertically into the reagent chamber 105 of the reagentcontainment section 80. Specifically, the center of the circular opening84 is substantially aligned along the vertical imaginary line 101 withthe midpoint 104′ of the nadir 104 in well 102. A slight degree ofmisalignment between the center of the circular opening 84 and themidpoint of the nadir 104 may be tolerated so long as the reagent probe38 can extend into a portion of well 102 near nadir 104. The tip of thereagent probe 38 will penetrate the upper surface of the reagent at apoint in its vertical travel parallel to the Z axis of the robot towardbase wall 90. Because the opening 84 is substantially aligned with thenadir 104, the tip of the reagent probe 38 will encounter an effectivedepth of residual reagent, as the reagent fluid level lowers to a pointsuch that the residual reagent in entirely contained in well 102, thatis sufficient for successful aspiration of a significant percentage ofthe total volume of reagent in the well 102, as well as close to 100% ofthe reagent in the entire reagent chamber 105. The reagent probe 38 istypically smaller diametrically than the opening 84. As a result, thereagent probe 38 may enter the opening 84 either parallel to theimaginary vertical line 101, or with a slight acute angle relative toline 101, and still travel in interior 105 toward and into well 102proximate to the nadir 104.

With reference to FIGS. 7 and 8, the horizontal flanges 106 a and 106 bproject outwardly from the exterior of the side walls 94, 96,respectively, and from portions of the front wall 98 of reagentcontainer 50. As described above, the flanges 106 a and 106 b engage atop surface 72 a of the platform 72 for suspending the base wall 90 ofthe reagent container 50 at or above the underlying upper surface of thebottom of chassis 14 when the reagent container 50 is supported withinone of the receptacles 76 in reagent rack 67. As a result, the uppersurface of the fluid, regardless of its fluid level within the reagentcontainment section 80, lies in a horizontal plane parallel with the X-Yplane of the robotic delivery system 22. The engagement between theflange 106 and the surface 72 a of the platform 72 surrounding thereceptacle 76 precludes the necessity for an adaptor or the like to holdthe reagent container 50 in the rack 67 for use in the autostainer 10.It is understood that the specific structure of flange 106, illustratedin FIG. 6, is not intended to be limiting of the invention and variousdifferent flange structures may be utilized for supporting reagentcontainer 160 in rack 67.

In one embodiment, the reagent containment section 80 and neck 82 areintegrally formed as a single-piece of a polymeric material by aconventional manufacturing process, such as blow molding, so that thereagent containment section 80 has a degree of flexibility and is eitheroptically translucent or transparent. In other embodiments, the reagentcontainment section 80 may also be fabricated from a relativelyinflexible material, such as a glass, which is usually opticallytranslucent or transparent. A portion of the front wall 98 includes aseries of vertically spaced, horizontally disposed, volume indicia orgraduations 108, which permit a visual determination of the approximatevolume of reagent held by the reagent containment section 80 in thoseembodiments in which the reagent containment section 80 is not opaque.However, the invention is not so limited and the reagent containmentsection 80 may be opaque for those reagent dispensing applications inwhich visual determination of the fluid level of reagent is unnecessaryor in which photosensitive reagents are stored.

With reference to FIGS. 6 and 8, the closure 86 of the reagent container50 is a two-piece assembly having a dropper cap tip 112 and a nozzle cap114. The dropper cap tip 112 includes a cylindrical side skirt 116, anannular collar 118, and a nozzle 120 having a fluid-directing passageway122 with a dispensing orifice 132. An inner surface of the side skirt116 includes a plurality of threads 123 that are threadingly engagedwith complementary threads 124 provided on an outer surface of neck 82.The annular collar 118 includes a channel 126 with a frustoconical innersealing surface 130 that engages a complementary frustoconical sealingsurface 128 provided about the mouth of the opening 84. The threadingengagement between the threads 123, 124 forces the frustoconical sealingsurfaces 128, 130 into sealing engagement when the closure 86 isattached to the neck 82. If the reagent container 50 is used in theautostainer 10, the dropper cap tip 112 and the tip cap 114 are removedso that the opening 84 is not occluded. The nozzle cap 114 isthreadingly received with a complementary threaded portion of the nozzle120. The dropper cap tip 112 and the nozzle cap 114 may each include aplurality of parallel axially-directed ridges that ease manual removalfrom the neck 82.

In a preferred embodiment and with reference to FIGS. 7 and 8, a pair ofprotrusions 134, 136, illustrated as being rounded, project outwardlyfrom the base wall 90. The protrusions 134, 136 are located proximate tothe rear wall 92 and have a spaced relative to the side walls 94, 96.The protrusions 134, 136 and an exterior seam 107 of the base wall 90are configured and positioned to contact a planar surface 110 when thereagent container 50 is placed thereupon. The seam 107 is located on theopposite side of base wall 90 from nadir 104 and has a similar length.The extent of the contacting engagement at the two points of protrusions134, 136 and along the seam 107 lends lateral stability to the reagentcontainer 50 when located on a planar surface 110, such as a laboratorybenchtop. As a result, the reagent container 50 may be used in theautostainer 10 and may also be used independent of the autostainer 10.Even if used in conjunction with the autostainer 10, the reagentcontainer 50 may be positioned on a planar surface 110 when not held inreagent rack 67. It is appreciated that the reagent container 50 of theinvention includes a nadir 104 for improving reagent removal and is alsocapable of being self-supporting on planar surface 110 without relyingupon a rack, such as reagent rack 67.

The reagent container 50 may also be used to deliver or dispense reagentmanually from the reagent containment section 80 and, when not in use,container 50 would rest in an upright position on planar surface 110supported thereupon by protrusions 134, 136 and seam 107. For manualdelivery of reagent, the reagent container 50 is held in a tilted or aninverted orientation. In embodiments in which the reagent containmentsection 80 is flexible, a compressive force applied to the reagentcontainment section 80 reduces the volume of the reagent containmentsection 80 and urges a volume of reagent to enter fluid-directingpassageway 122 for delivery from orifice 132. For those embodiments inwhich the reagent containment section 80 is not flexible, gravity causesa volume of reagent to be delivered from the dispensing orifice 132 ofthe inverted reagent container 50.

In an alternative embodiment and with reference to FIG. 7A, a reagentcontainer 50′ may include a single surface-contacting projection 137that replaces protrusions 134, 136 of reagent container 50 (FIG. 8). Theprojection 137 extends between the side walls 94, 96 and operates inconjunction with seam 107 to stabilize the reagent container 50′ againsttipping or otherwise deviating from an upright position, when container50′ is positioned on a flat surface, such as planar surface 110 (FIG.8). Specifically, the seam 107 and the projection 137 provide twosubstantially parallel and spaced-apart lines of contact with a surface,such as planar surface 110.

With reference to FIG. 9, the reagent container 50 includes atwo-dimensional bar code 140. Bar code 140 may be positioned on anysurface of container 50 accessible to a bar code reader, such as opticalreader 144 (FIG. 1A), but is typically positioned on the flat uppersurface 138 of the upper wall 88 and adjacent to the neck 82. Thetwo-dimensional bar code 140 is any two-dimensional array of opticallyreadable marks of any desired size and shape that are arranged in areference frame of rows and columns. Specifically, the readable marks ofthe two-dimensional bar code 140 contain reagent information encoded ina high density format, as understood by those of ordinary skill in theart, and may include dots, characters or any symbol or symbols capableof encoding information. Among the numerous high density formats arematrix symbologies, such as Data Matrix and Maxicode, andtwo-dimensional stacked symbologies, such as Code 49 and PDF417. Code 49is described, for example, in U.S. Pat. No. 4,794,239, Data Matrix codeis described, for example, in U.S. Pat. Nos. 4,939,354, 5,053,609, and5,124,536, Maxicode is described, for example, in U.S. Pat. Nos.4,874,936, 4,896,029, and 4,998,010, and PDF417 is described, forexample, in U.S. Pat. No. 5,243,655.

As known to one skilled in the art, reagent information that may beencoded into the two-dimensional bar code 140 includes, but is notlimited to, the lot number of the reagent, the identity of the reagent,the expiration date, reagent volume, reagent incompatibilities, and thelike. Such reagent information may be utilized for quality control andquality assurance documentation. It is further understood thattwo-dimensional bar codes 140 a, similar to two-dimensional bar codes140, may be applied to the reagent rack 67 adjacent to the appropriatereagent container 50, as shown in FIG. 5, and may contain readablereagent information.

With reference to FIG. 1A, the Z-head 24 of the autostainer 10 includesa two-dimensional optical reader 144, such as a charged coupled device(CCD) video camera or a CCD scanner, that is carried by the Z-head 24 ofthe X-Y-Z robotic delivery system 22. The reagent information associatedwith the two-dimensional bar code 140 is readable by optical reader 144.The optical reader 144 electro-optically scans the two-dimensional barcode 140 and generates a corresponding signal, which is provided to thecontrol system 28 where the signal is decoded and the reagentinformation stored for future use. The ability to retrieve and decodeinformation relating to the reagent from the two-dimensional bar code140 eliminates the need to manually enter the reagent information whenprompted by the control system 28.

Two-dimensional bar codes, such as two-dimensional bar code 140, mayalso be utilized in reagent packs (not shown) that contain variousreagents in discrete containment wells. Such reagent packs for use withan autostainer, such as autostainer 10, are described in patentapplication Ser. No. 09/483,148, incorporated by reference above.

With reference to FIG. 10 in which like reference numbers represent likefeatures in FIG. 6, another preferred embodiment of a reagent container150 of the present invention is shown. Reagent container 150 includes acircular opening 152 in the upper wall 138, an upwardly-projectingsealing lip 154 encircling the opening 152, and a frangible barrier 156covering the entrance to the opening 152. The frangible barrier 156 maybe formed, for example, from an aluminized polymer film. An outer rim ofthe frangible barrier 156 has a sealing engagement with the sealing lip154 so that the reagent in the interior 105 of the reagent containmentsection 80 is isolated from the surrounding environment. The center ofthe circular opening 152 is substantially aligned along verticalimaginary line 101 with the midpoint of the nadir 104. The frangiblebarrier 156 is broken or penetrated prior to either manual use ofreagent container 150 for the reagent held in or positioning reagentcontainer 150 in autostainer 10 (FIG. 1) to afford access to theinterior 105 for dispensing reagent therefrom.

With reference to FIG. 11 in which like reference numbers represent likefeatures in FIGS. 6-9, another preferred embodiment of a reagentcontainer 160 of the present invention is shown. A reagent containmentsection 161 of reagent container 160 includes an outwardly-projectingpair of side flanges 162, 164 adapted to engage the top surface 72 a ofthe platform 72 of rack 67 (FIG. 5) for suspending the base wall 90 ofthe reagent container 160 at or above the underlying upper surface ofthe bottom of the chassis 14 (FIG. 1) when the reagent container 160 issupported within one of the receptacles 76 in reagent rack 67. Sideflange 162 is projects outwardly from the front wall 98 and flange 164projects outwardly from rear wall 92 oriented with an opposite directionto side flange 162.

While the above description and accompanying drawings set forth variousembodiments of the invention, it will be apparent to those skilled inthe art that additions and modifications may be made without departingfrom the principles of the invention. Accordingly

What is claimed is:
 1. A reagent container configured for use in anautostainer having a probe, the container comprising: an upper wallhaving an access opening, a base wall, and a tubular side wall defininga reagent chamber, said tubular side wall including at least a firstwall and an opposite second wall interconnecting the base and upperwalls, said upper wall being spaced apart from said base wall along animaginary line passing through said base and upper walls, said base wallconverging inwardly and downwardly from said tubular side wall anddefining a well having a reduced horizontal cross-sectional arearelative to a horizontal cross-sectional area of said reagent chamberwith a nadir that is spaced from each of said first and second walls andis located closer to said first wall than said second wall, said nadirand said access opening being aligned with each other along saidimaginary line so that the probe entering said opening in a directionsubstantially parallel to said imaginary line is directed toward saidnadir.
 2. The reagent container of claim 1, wherein said upper wallincludes a neck having a passageway extending substantially parallel tosaid imaginary line, said access opening being formed in said neck andbeing substantially coextensive with the cross-sectional area of saidpassageway.
 3. The reagent container of claim 1, further comprising apair of opposite side flanges extending outwardly from said tubular sidewall of the container, with each of said side flanges being located aheight between the upper wall and the base wall.
 4. A reagent containerand rack assembly configured for use in an autostainer having a probe,comprising: a rack including: a platform; and at least one apertureformed in said platform; at least one reagent container configured to bereceived within said at least one aperture formed in said platform andincluding an upper wall having an access opening, a base wall, and atubular side wall defining a reagent chamber, said tubular side wallincluding at least a first wall and an opposite second wallinterconnecting the base and upper walls, said upper wall being spacedapart from said base wall along an imaginary line passing through saidbase and upper walls, said base wall defining a well having a reducedhorizontal cross-sectional area relative to a horizontal cross-sectionalarea of said reagent chamber with a nadir that is spaced from each ofsaid first and second walls and is located closer to said first wallthan said second wall, said nadir and said access opening being alignedwith each other along said imaginary line so that the probe enteringsaid opening in a direction substantially parallel to said imaginaryline is directed toward said nadir; and a pair of opposite side flangesextending outwardly from said tubular side wall of the container, witheach of said side flanges being located at a height between the upperwall and the base wall and being configured to engage said platform tosupport said at least one reagent container relative to said platform.5. The reagent container and rack assembly of claim 4, furthercomprising at least one support depending from said platform.